Apparatus for displacement of blood to mitigate peripheral nerve neuropathy

ABSTRACT

Embodiments of the present invention are directed to devices, systems and methods adapted for implementing intermittent displacement of blood to mitigate peripheral nerve neuropathy such as that induced by chemotherapeutic agents (i.e., chemotherapy-induced neuropathy (CIN)) that are administered to a patient. Such devices, systems and methods advantageously provide for precise, uniform and controlled blood flow occluding (and optionally blood displacing) compression along irregular surfaces of an appendage of a patient. Such precise, uniform and controlled blood occluding compression is imparted upon the epidermal and dermis skin layers within the aforementioned areas of a patient’s extremities to decrease the time that free nerve endings located in the epidermal and encapsulated nerve endings located in the dermis skin layers are exposed to nerve damaging chemotherapy chemicals, thereby substantially decreasing CIN caused by prolonged exposure to such chemicals.

CROSS-REFERENCE TO RELATED APPLICATIONS

This continuation patent application claims priority from co-pendingUnited States Non-provisional Patent Application having Serial No.16/834,807, filed 30-March 2020, entitled “Device, System and Method ForIntermittent Displacement of Blood to Mitigate Peripheral NerveNeuropathy”, having a common applicant herewith and being incorporatedherein in its entirety by reference.

United States Non-provisional Patent Application having Serial No.16/834,807 claims priority as a divisional from co-pending United StatesNon-provisional Patent Application having Serial No. 16/695,114, filed25-November 2019, entitled “Device, System and Method For IntermittentDisplacement of Blood to Mitigate Peripheral Nerve Neuropathy”, nowUnited States Patent No. 10,646,233 issued on 12-May 2020, having acommon applicant herewith and being incorporated herein in its entiretyby reference.

United States Non-provisional Patent Application having Serial No.16/695,114 claims priority from co-pending United States ProvisionalPatent Application having Serial No. 62/772,097, filed 28-November 2018,entitled “Peripheral Nerve Neuropathy Prevention by Intermittent BloodDisplacement”, having a common applicant herewith and being incorporatedherein in its entirety by reference.

United States Non-provisional Patent Application having Serial No.16/695,114 claims priority from co-pending United States ProvisionalPatent Application having Serial No. 62/781,516, filed 18-December 2018,entitled “Peripheral Nerve Neuropathy Prevention by Intermittent BloodDisplacement”, having a common applicant herewith and being incorporatedherein in its entirety by reference.

United States Non-provisional Patent Application having Serial No.16/695,114 claims priority from co-pending United States ProvisionalPatent Application having Serial No. 62/790,473, filed 10-January 2019,entitled “Peripheral Nerve Neuropathy Prevention by Intermittent BloodDisplacement”, having a common applicant herewith and being incorporatedherein in its entirety by reference.

United States Non-provisional Patent Application having Serial No.16/695,114 claims priority from co-pending United States ProvisionalPatent Application having Serial No. 62/857,454, filed 5-June 2019,entitled “Peripheral Nerve Neuropathy Prevention”, having a commonapplicant herewith and being incorporated herein in its entirety byreference.

FIELD OF THE DISCLOSURE

The disclosures made herein relate generally to treatment of cancerpatients, more particularly, to devices, systems and methods forintermittent displacement of blood to mitigate peripheral nerveneuropathy.

BACKGROUND

Peripheral neuropathy is a condition that affects nerves outside of thebrain and spinal cord (i.e., peripheral nerves). Peripheral neuropathyis often exhibited in patient’s hands and feet due to the vast amount ofnerves within such appendages. Peripheral neuropathy is known to affectboth free nerves endings within the epidermal skin layer (i.e.,unencapsulated nerves endings) and the nerve endings within the dermisskin layer (i.e., encapsulated nerves endings). Ailments in a portion ofthe body exhibiting peripheral neuropathy include, but are not limitedto, weakness, numbness and pain.

Peripheral neuropathy is known to be caused by a genetic condition or byone or more of many acquired conditions. One such acquired conditionthat is of particular interest is peripheral neuropathy resulting fromtreatment of cancer with one or more cytotoxic drugs causing the deathof healthy and malignant cells (i.e., commonly referred to aschemotherapy). In this manner, chemotherapy treatment of cancer thus isknown to cause chemotherapy-induced neuropathy (CIN)). CIN is severeside effect which occurs in a high majority of cancer patients aftertreatment with chemotherapeutics. Symptoms of peripheral neuropathy areusually mild to begin with and gradually worsen affecting frequently thehands, feet and lower legs. The soles of the feet and palms of the handsare most susceptible due to a high concentration of nerve endings (e.g.,as many as 200,000 nerve endings per sole).

Several chemotherapeutic agents are known to cause peripheralneuropathy. Examples of these chemotherapeutic agents include, but arenot limited to, vincristine and vinca alkaloids, platinum compounds(e.g., cisplatin, oxaliplatin, carboplatin, taxanes, epothilones,bortezomib), thalidomide and the like. Although the exact mode of actionin which these drugs cause nerve damage is not well known, it is thoughtthat the general mode of action disruption or alteration is signal flowwithin nerve cells. For example, platinum compounds such as oxaliplatinare thought to accumulate in the dorsal root ganglia and producehyperexcitability, whereas vinca alkaloids induce alterations in thecellular micro-tubuli structure leading to disruption of the axonalflow. The neurotoxicity of these agents is type and dose dependent, andseverity of neuropathy is generally increasing with duration oftreatment. CIN is known to be potentially irreversible. Chemotherapeuticagents are administered for a prescribed duration of time and/orquantity of the agent (i.e., an amount of delivery).

Currently, there are no effective treatment methods available to preventor cure CIN. Although some neuroprotective agents are thought todecrease the neurotoxicity of the chemotherapeutic agent, there is noconcrete clinical evidence supporting this data and the compounds toprevent CIN are known to cause side effects as well. For example,Omega-3 fatty acids are thought to have neuroprotective function inperipheral neuropathy induced by Paclitaxel in breast cancer patients,but these results have yet to be confirmed. As there are no knowncurative treatment options known for CIN sufferers and the use ofchemotherapeutics is often unavoidable for many cancer patients,prevention is a much more viable option than curative.

A recent attempt at prevention of CIN has been tried through inducedhypothermia using frozen gloves and socks. In such hypothermia treatmentof CIN, as disclosed in United Stated Patent Application Publication no.20150351957A1, the temperature of the foot and lower leg of a patientwas lowered, thereby producing slowed or restricted blood flow. Thisslowed or restricted blood flow is disclosed as reducing exposure to theharmful chemotherapeutic agents. However, with such hypothermiatreatment, there is still blood circulation such that chemotherapeuticagent exposure is only mildly limited. Another problem with thishypothermia treatment approach is the discomfort of hypothermia on thepatient for extended periods of time.

Compression therapy uses compression to intermittently displaced bloodfor enhancing blood circulation, diminishing post-operative pain andswelling, reducing wound healing time, and aiding in the treatment andhealing of stasis dermatitis, venous stasis ulcers, arterial anddiabetic leg ulcers, chronic venous insufficiency and reduction of edemain the lower limbs. Although compression therapy does provideintermittent displacement of blood, the intermittent displacement ofblood by application of pressure does not displace and limit bloodsupply to nerve endings to limit exposure to nerve endings from harmfulchemicals. Rather, it is intended to promote blood movement andcirculation by allowing blood to return to a treatment area and then torepeat the cycle frequently in a pulsing manner to artificially causethe movement of blood. In this respect, compression therapy does notlimit the exposure time of peripheral nerve endings to the chemicallycontaminated blood supply. Compression therapy does not provide for thedecrease in time nerve endings located in the dermis skin layers areexposed to nerve damaging chemotherapy agents to thereby decrease nervedamage caused by prolonged exposure to chemotherapeutic agents. As such,the functionality of compression therapy differs greatly from theintermittent displacement of blood from the dermis skin layers and thesimultaneous occlusion of capillary blood vessels suppling blood toselected dermis skin areas and to the nerve endings within the epidermaland dermis skin layer.

Therefore, a CIN treatment approach that provides for a more limitedexposure of the chemotherapeutic agents to peripheral nerve ending tosubstantially increasing the success of the prevention of CIN in amanner that overcomes drawbacks associated with conventional CINtreatment approaches would be advantageous, desirable and useful.

SUMMARY OF THE DISCLOSURE

Embodiments of the present invention are directed to devices, systemsand methods adapted for implementing intermittent displacement of bloodto mitigate peripheral nerve neuropathy such as that induced bychemotherapeutic agents (i.e., chemotherapy-induced neuropathy (CIN))that are administered to a patient over a prescribed amount of delivery(e.g., time for which a flow of chemotherapeutic agent is deliveredand/or volume of chemotherapeutic agent delivered). More specifically,embodiments of the present invention advantageously provide for precise,uniform and controlled blood flow occluding (and optionally blooddisplacing) compression along irregular surfaces of a human’s hands andfeet, including the spaces between the toes and fingers, the entiresole, sides of the soles, heals and toes of the foot and entire palm,fingers and palm sides of the hand. Such precise, uniform and controlledblood occluding compression (e.g., at least partially occluding bloodflow) is imparted upon the epidermal and dermis skin layers within theaforementioned areas of a patient’s extremities to decrease the timethat free nerve endings located in the epidermal and encapsulated nerveendings located in the dermis skin layers are exposed to nerve damagingchemotherapy chemicals, thereby substantially decreasing CIN caused byprolonged exposure to such chemicals. To further limit CIN, incombination with the aforementioned controlled blood-occludingcompression, embodiments of the present invention can be adapted tosimultaneously provide bio-available-oxygen through the epidermal skinto the peripheral nerve endings, the bio-available oxygen is carriedthrough the epidermal skin into the dermis layer within and aqueouspressure distribution medium. In this regard, embodiments of the presentinvention cause distributed compression that displaces and at leastpartially occludes the blood supply to the dermis and epidermal skinlayer that are highly susceptible to the damage caused bychemotherapeutic agents while actively mitigating tissue damageresulting from blood-occluding compression thereof.

In one or more embodiments other embodiments of the present invention, amethod for mitigating peripheral nerve neuropathy associated withchemotherapy treatment comprises administering a chemotherapeutic agentto a patient and exerting a compressive pressure on an appendage of thepatient. The chemotherapeutic agent is administered for a prescribedamount of delivery. Exerting the compressive pressure on the appendageof the patient is performed during the administering of at least aportion of the prescribed amount of delivery. The compressive pressureis exerted for causing at least one of a magnitude of the compressivepressure and a duration of time for the compressive pressure beingexerted to at least partially occlude blood flow into epidermal tissueof the appendage.

In one or more embodiments other embodiments of the present invention, asystem for mitigating peripheral nerve neuropathy associated withchemotherapy treatment comprises a compression exertion device having aninterior space adapted for receiving an appendage of a patient and apressure controller operably attached to the compression exertion deviceto cause a compression-inducing medium within the compression exertiondevice to exert compressive pressure on the appendage during at least aportion of a prescribed amount of delivery of a chemotherapeutic agentto the patient. The compression exertion device includes a sealingcomponent engageable with at least one of a portion of the appendage anda limb to which the appendage is attached when the appendage ispositioned within the interior space. The pressure controller beingoperably attached to the compression exertion device to cause thecompression-inducing medium within the compression exertion device toexert compressive pressure on the appendage includes causing at leastone of a magnitude of the compressive pressure and a duration of timefor the compressive pressure being exerted to at least partially occludeblood flow into epidermal tissue of the appendage. The pressurecontroller monitors administration of a chemotherapeutic agent to apatient to enable the compressive pressure to be provided as a functionof the administration of the chemotherapeutic agent to the patientduring a prescribed amount of delivery thereof.

In one or more embodiments other embodiments of the present invention, acompression exertion device is adapted for use with a peripheral nerveneuropathy system during chemotherapy treatment. The peripheral nerveneuropathy system is operably attachable to the pressure controller toenable pressurization of the compression exertion device for causingcompressive pressure to be exerted by the compression exertion device onan appendage of a patient. A pressure controller of the peripheral nerveneuropathy system monitors administration of a chemotherapeutic agent toa patient to enable the compressive pressure to be provided as afunction of the administration of the chemotherapeutic agent to thepatient during a prescribed amount of delivery thereof. The compressionexertion device comprises a compression body, a sealing component, anexpansion cavity and in at least one or more embodiments a quantity ofan aqueous compression inducing medium component capable of carryingbio-available oxygen through the epidermal skin layer into the dermisskin layer. The compression body including an interior space adapted forhaving the appendage of the patient engaged therein. The interior spaceencompasses at least a portion of an exterior surface of the appendage.The sealing component is engageable with at least one of a portion ofthe appendage and a limb to which the appendage is attached when theappendage is positioned within the interior space. The expansion cavityhas a wall thereof defining at least a portion of the interior space.The aqueous bio-available oxygen pressure distribution medium componentcan comprise nano oxygen bubbles, water, at least one penetrationenhancer.

In one or more embodiments, the compression exertion device and partsthereof can be made from a variety of man-made or natural rubbers,plastics and the like, having a hardness on the harness scale 00 of frombetween 10 to 90 and resistance to expansion from between about 10 mm hgand 155 mm hg.

In one or more embodiments, the compression exertion device may comprisea membrane for passage of oxygen while other parts may comprise wovennon-woven textile resistant to expansion.

In one or more embodiments, a component of the compression exertiondevice comprises an aqueous bio-available oxygen pressure distributionmedium comprised of a water solution, comprising nano oxygen bubbles(preferably smaller than 200 nm), a water solution comprising a mixtureof at least one or more of skin penetration enhancers including water,urea, glycol, ethanol, taurine to name a few and nano oxygen bubblestherein said pressure distribution medium providing thereby a safeepidermal penetrating aqueous oxygen carrier providing diffusion ofoxygen into the epidermal skin layer and into the dermis skin layer andtissues therein, an oxygen charged perfluorocarbon composition.

In one or more embodiments, the pressure distribution medium ispressurized from between about 10 mm hg and 50 mm hg and is in intimatecontact with the epidermal skin layer for the duration of the chemotherapy treatment without a cyclical operation.

In one or more embodiments, the aqueous pressure distribution medium ispressurized from between about 10 mm hg and 50 mm hg and is in intimatecontact with the epidermal skin layer for the duration of thechemotherapy treatment without a cyclical operation.

In one or more embodiments of the present invention, exerting thecompressive pressure is initiated prior to the administering of thechemotherapeutic agent and administering the chemotherapeutic agent isinitiated after blood flow into at least a portion the dermis tissue ofthe appendage is at least partially occluded.

In one or more embodiments of the present invention, the compressivepressure is released after the administering of the chemotherapeuticagent is initiated and the compressive pressure is reapplied after bloodflow is resumed through the appendage for a designated duration of time.

In one or more embodiments of the present invention, exerting thecompressive pressure on the appendage includes pressurizing acompression-inducing medium surrounding the appendage.

In one or more embodiments of the present invention, exerting thecompressive pressure on the appendage includes positioning the appendagewithin an interior space of a compression exertion device and deliveringa compression-inducing medium into at least one of the interior space ofthe compression exertion device and an expansion cavity of thecompression exertion device.

In one or more embodiments of the present invention, delivering thecompression-inducing medium includes delivering the compression-inducingmedium into the interior space of the compression exertion device andthe compression-inducing medium is an oxygen-carrying medium capable ofdiffusing oxygen into epidermal tissue of the appendage.

These and other objects, embodiments, advantages and/or distinctions ofthe present invention will become readily apparent upon further reviewof the following specification, associated drawings and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram view showing a perspective view showing amethod in accordance with an embodiment of the present invention forblood supply occluding compression of a treated appendage of a patientto mitigate chemotherapy-induced neuropathy within a treated appendage.

FIG. 2 is an illustrative view showing a compression exertion systemconfigured in accordance with one or more embodiments of the presentinvention.

FIG. 3 is an illustrative view showing a compression exertion device inaccordance with an embodiment of the present invention.

FIG. 4 is an illustrative view showing a compression body of thecompression exertion device of FIG. 3 .

FIG. 5 is a cross-sectional view showing a first construction of acompression exertion device in accordance with one or more embodimentsof the present invention.

FIG. 6 is a cross-sectional view showing a second construction of acompression exertion device in accordance with one or more embodimentsof the present invention.

FIG. 7 is a cross-sectional view showing a third construction of acompression exertion device in accordance with one or more embodimentsof the present invention

FIG. 8 is a cross-sectional view showing a fourth construction of acompression exertion device in accordance with one or more embodimentsof the present invention.

FIG. 9 is a cross-sectional view showing a fifth construction of acompression exertion device in accordance with one or more embodimentsof the present invention.

FIG. 10 is a cross-sectional view showing a sixth construction of acompression exertion device in accordance with one or more embodimentsof the present invention.

DETAILED DESCRIPTION

Devices, methods and systems configured in accordance with one or moreembodiments of the present invention are adapted to achieve intermittentblood flow occlusion and optional displacement of blood within anappendage of a patient (i.e., the treated appendage) to mitigateperipheral nerve neuropathy. Peripheral nerve neuropathy can be inducedby chemotherapeutic agents (i.e., chemotherapy-induced neuropathy(CIN)). Advantageously, such devices, methods and systems provide forprecise, uniform and controlled compression of the treated appendage.The objective of such treatment is to decreases the time that free nerveendings located in the epidermal and encapsulated nerve endings locatedin the dermis skin layers are exposed to nerve damaging chemotherapychemicals, thereby substantially decreasing CIN caused by prolongedexposure to such chemicals. To this end, devices, methods and systemsconfigured in accordance with one or more embodiments of the presentinvention provide distributed (e.g., uniform) compression of anappendage to at least partially occlude (i.e., inhibit) the supply ofblood to the dermis skin layer that are highly susceptible to the damagecaused by chemotherapeutic agents while actively mitigating tissuedamage resulting from the blood supply occluding compression. Partialblood flow occlusion can be such that a suitable degree of blood flow ismaintained such as to provide the required amount of blood flow forretaining cell life (e.g., blood flow of about 5% or less, 10% or less,25% or less about 5-10%, about 10-25%, less than about 25%, less thanabout 50%). This blood supply occluding compression can also be ofsufficient magnitude or duration to cause displacement of blood fromwithin the dermis skin layers of the treated appendage.

Underlying objectives of the methods for intermittent displacement ofblood within a treated appendage of a patient to mitigate CIN within atreated appendage in accordance with embodiments of the presentinvention (e.g., the method 100 disclosed below) include both providingdistributed compression of an appendage to at least partially occlude(i.e., inhibit) the supply of blood to the dermis skin layer that arehighly susceptible to the damage caused by chemotherapeutic agents andactively mitigating tissue damage resulting from the blood supplyoccluding compression. Both of these underlying objectives are relatedto sensory nerves located in the epidermal skin layer, which are alsoreferred to as fee nerve endings. When free nerve endings are notfunctioning properly, they produce symptoms such as numbness, pins andneedles, pain, tingling and burning, which are the symptoms accompaniedwith CIN. Although the epidermal skin layer does not have blood supply,it is nevertheless highly blood oxygen thirsty. These free orunencapsulated nerve ending extend from the border between the dermisand the epidermal skin layer up and into the epidermal skin layer. Thisbeing the case, it is believed that the area of joining between thedermis and the epidermal is where damage is caused by chemotherapeuticagents. The free nerve endings are not encapsulated as other peripheralnerves are and are much more susceptible to damage from thechemotherapeutic agents.

Immediately below the epidermis is the papillary dermis and papillaryplexus and the superficial arteriovenous plexus (capillary bed). Thepapillary dermis tissue is where blood from the capillary arteriesenters and gaseous exchanges take place supplying oxygen to theperipheral nerve endings. Additionally, blood in the papillary dermistissue can scavenge for toxins and carry the toxins to other organs forremoval. Blood exits the arterial capillaries at about 35 mm hg and intothe surrounding tissue, the pressure in this surrounding tissue is about25 mm hg. Blood from the surrounding tissue reenters the venouscapillaries because, at that point, the hydrostatic pressure in theveins is about 18 mm hg while the pressure in the surrounding tissue isabout 25 mm hg. The surrounding tissue where this blood, gas and toxinexchange takes place is where it is believed that the chemo toxins canbuild up and seep in alongside the free nerve endings within theepidermis skin layer and cause the damage to the very delicate nerveending in this area.

To minimize chemo toxic blood (i.e., blood containing chemotherapeuticagents) in contact with the fragile nerve ending and provide a supply ofoxygen simultaneously to the tissues and nerve endings, implements inaccordance with embodiments of the present invention (e.g., devices,systems and methods) provide for uniform compression of the tissuessurrounding the nerve endings. The pressure applied to the surroundingtissue to prevent mechanical or other damage to the nerve ending shouldbe at or below the arterial capillary pressure of 35 mm hg. Two thingshappen when pressure is applied: first, any blood containingchemotherapeutic agents is displaced through the venous wall and isreturned to other organs for removal and, second, the pressure beingintermittently supplied equals the pressure in the capillary arteries of35 mm hg. This will prevent further ingress of chemo blood toxins intothe surrounding issue. In response to the pressure being intermittentlyreleased, blood containing chemotherapeutic agents will fill into thesurrounding tissue for oxygenation of the tissues and nerve endings. Aspressure is applied and blood is displaced in the tissue, the majorityof chemotherapeutic agents will pass with the blood into the venouscapillaries and the cycles continue as necessary.

Referring to FIG. 1 , a method 100 for blood supply occludingcompression of a treated appendage of a patient to mitigate CIN within atreated appendage. To this end, the method 100 provides for precise,uniform and controlled blood supply occluding compression of theepidermal and dermis skin layers of the treated appendage. This precise,uniform and controlled blood supply occluding compression inhibits thesupply of blood to the dermal layers that are highly susceptible to thedamage caused by chemotherapeutic agents. The method 100 is adapted toprovide such exerted blood supply occluding compression in a manner thatlimits tissue damage resulting from the exerted blood supply occludingcompression, thereby substantially decreasing CIN caused by prolongedexposure of nerves of the treated appendage to chemotherapeutic agents.The blood supply occluding compression can be of sufficient magnitudeand/or duration so as to at least partially occlude blood flow into theappendage and to displace blood from within at least a portion of thedermis skin layer of the appendage.

The method 100 begins with an operation 102 of engaging an appendagewithin an interior space of a compression exertion device beingperformed. The operation 102 is performed in conjunction with (e.g.,prior to or contemporaneously with) initiation of a chemotherapytreatment session of the patient. For example, one or both feet and/orhands of the patient can be placed within an interior space of one ofmore compression exertion devices. As discussed below, the compressionexertion device(s) is(are) adapted for enabling a gaseous and/or fluidcompression inducing medium to impart a distributed and uniformcompressive force onto an exterior surface of the appendage(s).

Prior to or in combination with engaging an appendage within an interiorspace of a compression exertion device, an outermost protective skinlayer of the appendage (generally referred to as the Stratum Corium) ismodified for promoting transfer of gaseous and/or liquid materialtherethrough. Examples of such Stratum Corium modification include, butare not limited to, pre-soaking the treated area of appendage in anaqueous solution of water comprising one or more penetration enhancers,microscopic, nano sized oxygen bubbles, for a period of time to increasethe oxygen levels within the epidermal skin layer and to saturate theepidermal layer with oxygenated water prior to commencement oftreatment. Adhesive tape stripping, micro-punctures, micro dermalabrasions, chemical peels and the like are other pre-treatments to thestratum corium. The stratum corium comprises between 5-10% water but canbe saturated up to 40% or more water. Diffusion of gases through theskin has been shown in multiple studies to increase exponentially withincreased water content of the stratum corium, increasing the diffusionrate of gases 2-fold to 4-fold when wet. Modification therefore of thestratum corium for promoting transfer of gaseous and/or liquid materialtherethrough is beneficial to enable an oxygen enriched flowable mediumthat delivers oxygen into the dermis skin layer providing oxygen to bereceived by nerve endings and other cellular mater within the appendage.As discussed below in greater detail, such oxygen delivery limitsoxygen-deprived necrosis (i.e., tissue damage) resulting from bloodsupply occluding compression of the method 100.

After the appendage is placed within the compression exertion device andin combination with chemotherapy treatment, an operation 104 of causingthe compression exertion device to exert a distributed compressive forceonto an exterior surface of the appendage is performed for providing acurrent instance of blood supply occluding compression on the appendage.To this end, in one or more embodiments of the present invention, agaseous and/or fluid compression-inducing medium can be delivered tocompression exertion device and such compression-inducing medium eitherdirectly or indirectly causing a generally uniform compressive force tobe exerted onto an exterior surface of the appendage that is locatedwithin the interior space of the compression exertion device. Thecompression-inducing medium may be an oxygen carrying medium, asdiscussed below in greater detail.

In one or more preferred embodiments, the current instance of bloodsupply occluding compression pressure is induced for a period, forexample 1 minute, before administration of chemotherapy. Preferably, butnot necessarily, the blood supply occluding compression of the appendageis of a sufficient magnitude to also cause partial displacement of bloodfrom within the dermis skin layer of the appendage. For example, thecompression-inducing medium can be maintained at an applied pressurepreferably of between about 10 mm hg to about 25 mm hg and morepreferred from between about 25 mm hg to about 50 mm hg. Displacement ofblood from within the appendage advantageously limits exposure of nervetissue (and skin tissue in general) to blood containing chemotherapeuticagents, thereby advantageously mitigating CIN within the appendage.

In one or more embodiments, exerting the distributed compressive forceonto the exterior surface of the appendage can include delivering oxygen(e.g., dissolved oxygen in thermally conditioned water) to skin tissueof the appendage. Delivering oxygen to the skin tissue serves tomaintain life of skin tissue cells during the blood supply occludingcompression and possible displacement of blood from within the dermisskin layer of the appendage, thus limiting oxygen-deprived necrosis. Tothis end, oxygen delivery can be provided for by diffusion (i.e.,transfer) of oxygen via an oxygen enriched flowable medium such as afluid (e.g., a gas of a liquid), a gel, a cream, a serum, a paste or acombination thereof. The oxygen enriched flowable medium can be anoxygen carrier that can include one or more penetration enhancers suchas those generally regarded as safe by the FDA (e.g., vitiman E,transcutol, oleic acid, glycols, ethanol, terpines, menthols,1,8-cineole d-limolene phospholipids and water), one or moreperfluorocarbons (e.g., perfluorohexane, perfluoroperhydrophenanthreneperfluorodecalin, fiflow perfluorocarbon products) one or morepharmaceutical grade emulsifier, surfactants and the like. The oxygenenriched flowable medium facilitates oxygen diffusion into and throughthe stratum corium of the patient’s skin into the dermis skin layer,thereby facilitating diffusion of oxygen supply to peripheral nerveendings and skin tissue during the blood supply occluding compression.

In some embodiments, oxygen diffusion can be via direct contact of theoxygen enriched flowable medium with the patient’s skin, such as by theoxygen enriched flowable medium being pressurized to cause the bloodsupply occluding compression within the compression exertion device andbeing in direct contact with the appendage. In other embodiments, oxygendiffusion can be via indirect contact of the oxygen enriched flowablemedium with the patient’s skin, such as by the oxygen enriched flowablemedium being subjected to exerted pressure that causes the blood supplyoccluding compression within the compression exertion device andseparated from a surface of the appendage by a membrane through whichoxygen can pass. In yet other embodiments, oxygen diffusion can be viadirect contact of the oxygen enriched flowable medium with the patient’sskin, but where the oxygen enriched flowable medium is in indirectcontact with a compressive force inducing fluid within the compressionexertion device. Flowability of the oxygen enriched flowable mediumunder pressure enables the oxygen enriched flowable medium to beself-contouring in regard to a contour of the exterior surface of theappendage, which serves to promote equally distributed blood supplyoccluding compression and oxygen diffusion into and through the stratumcorium of the patient’s skin.

Water including dissolved oxygen has been shown to substantially supplyoxygen into the epidermis up to 700 microns deep when soaking feet inoxygenated water. With the edition of one or more water compatible andgenerally excepted as safe (e.g., by the FDA standard(s)) skinpenetration enhancers, oxygen is able to penetrate the epidermal andinto the dermis skin layer and tissues, allowing oxygen to be suppliedto tissues and nerves during blood supply occluding compression. Animportant aspect of a compression-inducing medium utilized withimplements in accordance with embodiments of the present invention canbe its oxygen carrying capacity of some components such as water,fluorocarbons with excellent gas exchanging capacity oxygen and carbondioxide. This oxygen carrying capacity makes compression-inducing mediumcomprising these components an ideal aqueous pressure distributionmedium.

In one or more embodiments, the blood supply occluding compression canbe imparted through a quantity (e.g., predetermined quantity) offlowable medium such as, for example, an aqueous bio-available oxygen ina liquid medium that is applied to the appendage prior to or as a resultof being engaged within the interior space of the compression exertiondevice. The quantity of flowable medium can be a metered quantity ofaqueous medium that is determined based upon at least one of a volume ofthe interior space of the compression exertion device, a size of thepatient’s appendage, an efficiency by which oxygen is capable of beingtransferred into the patient’s appendage, a diffusion rate enabled by amembrane through which the oxygen is diffused, or combination thereof.

During a current instance of the distributed compressive force beingexerted onto the exterior surface of the appendage, an operation 106 ofimplementing a next instance of blood supply occluding compression onthe appendage, where such next instance now become the current instance.To this end, implementing the next instance of blood supply occludingcompression can include monitoring of a pressure exerted on theappendage by the compression-inducing medium and thereafter controllingsuch pressure to terminate the blood supply occluding compression for adesignated period of time and then re-apply pressure for causing bloodsupply occluding compression. In this manner, after a prescribed periodof time and/or after a level of blood oxygen in the appendage decreasesto a prescribed level, pressure exerted on the appendage via thecompression-inducing medium can be reduced or eliminated for aprescribed period or time to allow blood flow to the appendage and thenpressure exerted on the appendage via the compression-inducing mediumcan be re-applied. To prevent oxygen deprived tissue necrosis, thisintermittent application of pressure can be repeatedly carried outthroughout the administration of chemotherapy treatment at uniform(e.g., solely time-based) or non-uniform intervals (e.g., at leastpartially blood oxygen-level based). In a specific implementation ofsuch intermittent pressure application, blood supply occludingcompression is maintained for a period preferably of from about 3minutes to about 10 minutes and still more preferred from about 10minutes to about 30 minutes and still more preferably from between about30 minutes to and about 60 minutes and still more preferably from about60 minutes to about 90 minutes after initiation of a current instance ofblood supply occluding compression.

As disclosed above, exerting the distributed compressive force onto theexterior surface of the appendage can include delivering oxygen viadissolved oxygen in thermally conditioned water to skin tissue of theappendage. Water is a well-known and often used penetration enhancer andeasily penetrates into the stratum corium. Oxygen is easily dissolvedinto water but will not stay suspended for long periods of time.Recently it has been discovered that nano sized oxygen bubbles can alsobe easily suspended in water with the added benefit that the oxygencontent of nano sized oxygen bubbles in water is greatly enhanced,additionally the properties of nano sized bubbles are charged having anegatively charged exterior and the buoyancy is also greatly reduced,therefore time that nano sized oxygen bubbles are suspended in the watercan be months instead of hours. Therefore, water saturated with nanosizes oxygen bubbles and one or more water compatible penetrationenhancers and utilized as an aqueous pressure distribution mediumcomponent of the compression exertion device would be highly beneficialand advantageous in suppling oxygen to peripheral nerves and tissues inthe epidermal and dermis skin layers. In one or more embodiments, thethermally conditioned water including the nano sized oxygen bubbles andcan be replaced between instances of blood supply occluding compression.Such replacement will allow replenishment of oxygen available fordiffusion through the stratum corium and into the dermis skin layer.

FIG. 2 shows a compression exertion system 200 configured in accordancewith one or more embodiments of the present invention. The compressionexertion system 200 includes a compression exertion device 202 operablyconnected to a pressure controller 204. The compression exertion device202 and the pressure controller 204 are jointly configured for enablingpressurization of a compression-inducing medium within an expansioncavity of the compression exertion device. A wall of the expansioncavity can at least partially define an interior space of thecompression exertion device and serve as an electrode for electricalcommunication through the appendage 1. The pressure controller 204carries out system-managed pressurization of a compression-inducingmedium within an expansion cavity of the compression exertion device 202(e.g., via pressurized delivery of the compression-inducing medium) forcausing blood supply occluding compression of an appendage 1 disposedwithin the compression exertion device 202. In one of more embodiments,the pressure controller 204 includes a programmable controlled pressuresource that is fluidly interconnected to the compression exertion device202 for enabling the pressure controller to carry out the system-managedpressurization of a compression-inducing medium within an expansioncavity of the compression exertion device 202 in the manner set forthabove in reference to the method 100 discussed above.

Referring to FIGS. 2-4 , the compression exertion device 202 can includea compression body 206 and an outer body 208. The compression body 206is fluidly interconnected with the pressure controller 204. Such fluidinterconnection enables communication of a compression-inducing mediumbetween the pressure controller 204 and the compression body 206 forcausing the aforementioned blood supply occluding compression of theappendage 1 disposed within the compression exertion device 202.

The outer body 208 has an interior space 210 within the which thecompression body 206 is located. The outer body 208 can serve to protectthe compression body 206 from damage by physical contact with externalitems and to constrain expansion of an exterior surface 212 of thecompression body 206 during application of blood supply occludingcompression of the appendage 1. To this end, the outer body 208 caninclude one or more securement components (e.g., securable flaps) forallowing the compression body 206 to be fixedly disposed within theinterior space 210 of the outer body 208. To constrain expansion of theexterior surface 212 of the compression body 206 during application ofblood supply occluding compression of the appendage 1, the body 208 canbe made from materials exhibiting limited or no deformation, expansionand/or elongation to thereby allow the outer body 208 to serve as anexpansion limiting impediment relative to the compression body 206 whenthe compression body 206 is subject to pressurization by delivery of thecompression-inducing medium via the pressure controller 204. One exampleof such a material is Cordura brand nylon.

The compression body 206 includes an interior space 214 adapted forhaving an appendage of a patient engaged therein. In one or moreembodiments, the interior space 214 of the compression body 206 can beconfigured for having a foot engaged therein (e.g., a boot, shoe orslipper). In one or more other embodiments, the interior space 206 ofthe compression body 206 can be configured for having a hand engagedtherein (e.g., a glove or mitten). The pressure controller 204 isfluidly and operably connected to the compression body 206 through oneor more fluid transfer conduits 216, 218, 220. Each of the fluidtransfer conduits 208, 210, 212 can be tubing or other elongatedconveyance structure through which a gaseous and/or liquid (i.e., fluid)compression-inducing medium can flow for enabling the compressionexertion device 202 to provide distributed pressure onto the appendage 1for exerting blood supply occluding compression. Each of the fluidtransfer conduits 216, 218, 220 can provide for flow ofcompression-inducing medium to the compression body 206, flow ofcompression-inducing medium from the compression body 206, ventilationof fluid from the compression body 206, or a combination thereof.

Referring now to FIG. 5 , a first construction of a compression exertiondevice in accordance with one or more embodiments of the presentinvention (i.e., compression exertion device 302) is shown, which can beused as a compression exertion device discussed above in reference toFIGS. 1-4 . The compression exertion device 302 includes a compressionbody 306 and an outer body 308. The outer body 308 has an interior space310 within the which the compression body 306 is located. The outer body308 can serve to protect the compression body 306 from damage byphysical contact with external items and to constrain expansion of thecompression body 306 during application of blood supply occludingcompression of an appendage 1 within an interior space 314 of thecompression body 306.

The compression body 306 includes an outer enclosure 320, a pressuredistribution article 322, a compression sealing bladder 324, a sealingcomponent 326, a bladder connector 328 and an expansion cavity connector330. The outer enclosure 320, the pressure distribution article 322, thecompression sealing bladder 324 and the sealing component 326 jointlydefine an expansion cavity 332. A wall of the expansion cavity can atleast partially define an interior space of the compression exertiondevice and serve as an electrode for electrical communication throughthe appendage 1. A compression-inducing medium 334 can be delivered intothe expansion cavity 332 through the expansion cavity connector 330 forenabling the compression exertion device 302 to provide distributedpressure onto the appendage 1 for exerting blood supply occludingcompression thereon. Such blood supply occluding compression is exertedon the appendage 1 directly by the pressure distribution article 322under pressure provided by the compression-inducing medium 334 withinthe expansion cavity 332. The compression sealing bladder 324 can beinflated by a fluid disposed therein through the bladder connector 328,thereby sealing the sealing component 326 against an exterior surface ofthe appendage 1 to inhibiting flow of pressure distribution medium 334from within a space jointly defined by the exterior surface of theappendage 1, the sealing component 326 and the outer enclosure 320.Inflation of the compression sealing bladder 324 may also cause thecompression sealing bladder 324 to become engaged with the outer body308. Optionally, the compression sealing bladder 324 may be bonded tothe outer body 308.

It is disclosed herein that the pressure distribution article 322 ispreferably formed from a material having properties enabling it to beconformed to a surface contour of the appendage 1. The pressuredistribution article 322 preferably has a thickness and hardness thatenables pressure within the expansion cavity 332 to be uniformlydistributed onto the exterior surface of the appendage 1. To this end,in one or more embodiments, the pressure distribution article 322 iscomprised of a moldable, substantially supple material conforming underpressure to irregular surface features of the appendage 1. One specificexample of such a moldable, substantially supple material is anon-hardening moldable putty fitted about irregular surface features ofthe appendage 1. Another specific example of such a moldable,substantially supple material is a two-part reactant liquid rubbermolded to conform about irregular surface features of the appendage 1.

In one or more embodiments, the material from which the pressuredistribution article 322 is made is a polymeric or elastomeric materialhaving a Shore hardness on the 00 scale of from about 0 to about 90, andmore preferably from between about 0 and about 40 and still morepreferably from between about 40 and about 80. The polymeric orelastomeric material can be of a material composition comprising anynumber of resilient materials compositions such as, by way of example,polysulfide, silicon, latex, polyurethane, polysulfide, and urethane.

The pressure distribution article 322 may be configured to provide foroxygen diffusion into tissue of the appendage 1. To this end, in one ormore embodiments, the pressure distribution article 322 may include anopen pore structure extending throughout. The open pore structure may beloaded with an oxygen carrying medium comprising a paste, cream, gel,serum, fluid or the like. In use, pressure exerted on the pressuredistribution article 332 (e.g., by the compression-inducing medium 334)may compress the pressure distribution article 332 and cause dispersionof the oxygen carrying medium out of the open porous structures and ontothe surface area of the epidermal skin. In this regard, oxygen from theoxygen carrying medium is thereby diffused through the stratum coriuminto the dermis skin layer and thereby diffused oxygen is supplied tothe peripheral nerves and tissues of the dermis skin layer.

Referring now to FIG. 6 , a second construction of a compressionexertion device in accordance with one or more embodiments of thepresent invention (i.e., compression exertion device 402) is shown,which can be used as a compression exertion device discussed above inreference to FIGS. 1-4 . The compression exertion device 402 includes acompression body 406 and an outer body 408. The outer body 408 has aninterior space 410 within the which the compression body 406 is located.The outer body 408 can serve to protect the compression body 406 fromdamage by physical contact with external items and to constrainexpansion of the compression body 406 during application of blood supplyoccluding compression of an appendage 1 within an interior space 314 ofthe compression body 406.

The compression body 406 includes an outer enclosure 420, a compressionsealing bladder 424, a sealing component 426, a bladder connector 428,an expansion cavity connector 430 and a vent connector 431. Theappendage 1, the outer enclosure 420, the compression sealing bladder424 and the sealing component 426 jointly define an expansion cavity432. A wall of the expansion cavity can at least partially define aninterior space of the compression exertion device and serve as anelectrode for electrical communication through the appendage 1. Acompression-inducing medium 434 can be delivered into the expansioncavity 432 through the expansion cavity connector 430 for enabling thecompression exertion device 402 to provide distributed pressure onto theappendage 1 for exerting blood supply occluding compression thereon.Such blood supply occluding compression is exerted on the appendage 1directly by the compression-inducing medium 434. The compression sealingbladder 424 can be inflated by a fluid disposed therein through thebladder connector 428, thereby sealing the sealing component 426 againstan exterior surface of the appendage 1 to inhibiting flow or movement ofcompression-inducing medium 434 from within the expansion cavity 432.Inflation of the compression sealing bladder 424 may also cause thecompression sealing bladder 424 to become engaged with the outer body408. Optionally, the compression sealing bladder 424 may be bonded tothe outer body 408 and the sealing component 426 bonded to thecompression sealing bladder 424.

The compression-inducing medium 434 may be an aqueous oxygen carryingmedium. In this regard, the compression-inducing medium 434 can beconfigured to provide for oxygen diffusion into tissue of the appendage1 carried within the aqueous oxygen carrying medium into tissues of theappendage. In use, pressurization of the compression-inducing medium 434causes intimate engagement of the compression-inducing medium 434 toenable such oxygen diffusion diffused through the stratum corium intothe dermis skin layer and thereby diffused oxygen is supplied to theperipheral nerves and tissues of the dermis skin layer.

Referring now to FIG. 7 , a third construction of a compression exertiondevice in accordance with one or more embodiments of the presentinvention (i.e., compression exertion device 502) is shown, which can beused as a compression exertion device discussed above in reference toFIGS. 1-4 . The compression exertion device 502 includes a compressionbody 506 and an outer body 508. The outer body 508 has an interior space510 within the which the compression body 506 is located. The outer body508 can serve to protect the compression body 506 from damage byphysical contact with external items and to constrain expansion of thecompression body 506 during application of blood supply occludingcompression of an appendage 1 within an interior space 514 of thecompression body 506.

The compression body 506 includes an outer enclosure 520, stratum coriumpiercing structure 523, a sealing component 526, an expansion cavityconnector 530 and a vent connector 531. The appendage 1 and the outerenclosure 520 jointly define an expansion cavity 532. A wall of theexpansion cavity can at least partially define an interior space of thecompression exertion device and serve as an electrode for electricalcommunication through the appendage 1. The outer enclosure 520 includesa perimeter edge portion 533 configured in a ‘U-shaped manner’ to enablepressurization of compression-inducing medium 534 delivered into theexpansion cavity 532 through the expansion cavity connector 530 tocreate a sealing structure between the outer enclosure 520 and thesealing component 526, with the sealing component 526 providing a sealwith the appendage 1. Such delivery of the compression-inducing medium534 into the expansion cavity 532 also enables the compression exertiondevice 302 to provide distributed pressure onto the appendage 1 forexerting blood supply occluding compression thereon. Such blood supplyoccluding compression is exerted on the appendage 1 directly by thecompression-inducing medium 534.

The compression-inducing medium 534 may be an aqueous oxygen carryingmedium. In this regard, the compression-inducing medium 534 can beconfigured to provide for oxygen diffusion into tissue of the appendage1 carried within the aqueous oxygen carrying medium into tissues of theappendage. In use, pressurization of the compression-inducing medium 534causes intimate engagement of the compression-inducing medium 534 toenable such oxygen diffusion to be diffused through the stratum coriuminto the dermis skin layer and thereby diffused oxygen is supplied tothe peripheral nerves and tissues of the dermis skin layer. To promoteoxygen diffusion, pressurization of compression-inducing medium 534delivered into the expansion cavity 532 having a stratum corium piercingstructure 523 fixed to the epidermal skin portion of an appendage can bestructured to permit diffusion of oxygen therethrough. To this end, thecompression-inducing medium 534 may be an aqueous oxygen carryingmedium. In this regard, the compression-inducing medium 534 can beconfigured to provide for oxygen diffusion into tissue of the appendage1. In use, pressurization of the compression-inducing medium 534 causesintimate engagement of the compression-inducing medium 534 to enablesuch oxygen diffusion diffused through the stratum corium (e.g.,including through one or more passages through the stratum coriumpiercing structure 523) into the dermis skin layer and thereby diffusedoxygen is supplied to the peripheral nerves and tissues of the dermisskin layer. In one or more embodiments, the stratum corium piercingmicro punctures may be pre-formed prior to insertion of an appendagewithout the piercing device being attached to the epidermal skin). Awall of the expansion cavity can at least partially define an interiorspace of the compression exertion device and serve as an electrode forelectrical communication through the appendage 1.

Referring now to FIG. 8 , a fourth construction of a compressionexertion device in accordance with one or more embodiments of thepresent invention (i.e., compression exertion device 602) is shown,which can be used as a compression exertion device discussed above inreference to FIGS. 1-4 . The compression exertion device 602 includes acompression body 606 and an outer body 608. The outer body 608 has aninterior space 610 within the which the compression body 606 is located.The outer body 608 can serve to protect the compression body 606 fromdamage by physical contact with external items and to constrainexpansion of the compression body 606 during application of blood supplyoccluding compression of an appendage 1 within an interior space 614 ofthe compression body 606.

The compression body 606 includes an outer enclosure 620, a pressuredistribution article 622, a sealing component 626, a first expansioncavity connector 630, a second expansion cavity connector 631 and acavity partition 635. The outer enclosure 620 includes a perimeter edgeportion 633 configured in a ‘U-shaped manner’ to enable pressurizationof compression-inducing medium delivered into the expansion cavity 632through the first expansion cavity connector 630 to create a sealingstructure between the outer enclosure 620 and the sealing component 626,with the sealing component 626 providing a seal with the appendage 1. Awall of the expansion cavity can at least partially define an interiorspace of the compression exertion device and serve as an electrode forelectrical communication through the appendage 1. The outer enclosure620 and the cavity partition 635 jointly define an expansion cavity 632.The pressure distribution article 623 and the cavity partition 635jointly define an oxygen-carrying medium cavity 637. An oxygen-carryingmedium can be provided in the oxygen-carrying medium cavity 637, withthe pressure distribution article 622 being configured for enablingpassage of oxygen from the oxygen-carrying medium through the pressuredistribution article 622 for diffusion into tissue of the appendage 1that is engaged with the pressure distribution article 622. A cavitypartition in accordance with embodiments of the present invention canhave passages for allowing transmission of the compression-inducingmedium therethrough, be a membrane enabling transmission of oxygen of acompression-inducing medium therethrough, or a combination thereof.

As shown in FIG. 9 , in one or more other embodiments, the compressionexertion device 602 is provided with at least two expansion cavities forproviding two separate pressure-inducing mediums, i.e., a first pressureinducing medium within the first expansion cavity 632 and a secondpressure inducing medium within the oxygen-carrying medium cavity 637(i.e., a second expansion cavity). The compression exertion device 602can further include a third first expansion cavity connector 641 and afourth expansion cavity connector 642. The outer enclosure 620 and thecavity partition 635 jointly define the expansion cavity 632. A wall ofthe expansion cavity can at least partially define an interior space ofthe compression exertion device and serve as an electrode for electricalcommunication through the appendage 1. The cavity partition 635 and asurface of the appendage 1 jointly define the oxygen-carrying mediumcavity 637 (i.e., the second expansion cavity). In this respect,different pressure-inducing mediums and associated delivery pressurescan be used for exerting blood supply occluding compression on theappendage 1 and for delivering oxygen (e.g., bio-available dissolvedoxygen or nano oxygen bubble water solution) to the appendage via itsepidermal skin layer.

A pressure distribution medium comprised of a bio-available dissolvedoxygen or nano oxygen bubbles in an aqueous solution can be introducedthrough the first expansion cavity connector 630 into the first 632 andpressurized to a first pressure of, for example, from between about 10mm hg and 25 mm hg for the duration of the chemotherapy treatment. Thefirst pressure preferably provides a minimal pressure for displacingblood from the uppermost portion of the dermis skin layer. A compressioninducing medium of air, gas or liquid can be introduced into the secondexpansion cavity 637 through the third expansion cavity connector 641and is pressurized, for example, from between about 10 mm hg and 50 mmhg for a predetermined time preferable, for example, from between about3 and 10 minutes, and more preferable from between about 10 and 30minutes and still more preferably from between about 30 and 60 minutesand even more preferably from between about 60 to 120 minutes.

The pressure within the second expansion cavity 637 is cycled from ahigh pressurized state to a non-pressurized state. During thepressurized state, pressure within the second expansion cavity 637expands the cavity partition 635 between the first and second expansioncavities 632, 637, thereby increasing the pressure impinged on theepidermal skin layer through the pressure distribution medium containingbio-available dissolved oxygen or nano oxygen bubbles in an aqueoussolution, equal to the pressure within the second expansion cavity.During the non-pressurized cycle of the second expansion cavity 637, thepressure impinged on the first expansion cavity 632 from the secondexpansion cavity 637 can be reduced to atmospheric pressure and thepressure within the first expansion cavity 632 decreases and remainsequal to the pressure applied within the first expansion cavity 632prior to application of the higher impingement pressure in the secondexpansion cavity 637. In this manner, a minimal pressure is applied tothe epidermal skin layer providing at least partial blood displacementfrom the dermis shin layer throughout the duration of the chemotherapytreatment.

In one or more embodiments, the same underlying treatment approachdescribed above for the first and second expansion cavities 632, 637 canbe practiced with a single expansion cavity. In such one or moreembodiments, the second expansion cavity 637 has bio-available oxygenpressure distribution medium delivered thereto with a controllablepressure source. The pressures can be cycled from a minimal pressurestate and then increased to the high-pressure state with the use ofprogramable precision controlled medical pumps, provided by numerousmedical device manufactures.

Referring to FIG. 10 , in one or more embodiments, a fifth constructionof a compression exertion device in accordance with one or moreembodiments of the present invention (i.e., compression exertion device702) is shown, which can be used as a compression exertion devicediscussed above in reference to FIGS. 1-4 . The compression exertiondevice 702 includes an outer body 708 that can also serve as acompression body of the compression exertion device 702. The compressionexertion device 702 can be provided prepackaged in kit form thatincludes a pressure distribution medium 747 (e.g., a bioavailable oxygenpressure distribution medium) metered onto an interior surface of theouter body 708, whereby the pressure distribution medium 747 is packagesealed within an interior space 714 of the compression exertion device702. Where the pressure distribution medium 747 is a bioavailable oxygenpressure distribution medium, a removable packaging substrate 713 suchas, for example, made of either one of a impervious film, foil,cellophane, plastic and the like is provided over an exposed surface ofthe pressure distribution medium 747 to limit escape of oxygen from inthe bioavailable oxygen pressure distribution medium. A removal member719 (e.g., a cord, strap or the like) is attached to a lower extreme endportion of the removable packaging substrate 713 for easy removal of thepackaging substrate 713. Alternatively, removal of the packagingsubstrate 713 can expose an oxygen gas pervious membrane on top of thepressure distribution medium 747 through which oxygen molecules canflow. The pressure distribution medium 747 defines a pressuredistribution medium space 739 within the interior space 714 of thecompression exertion device 702.

The compression exertion device 702 can include a gas-charging inletconnector 717 for charging the interior space 714 of the compressionexertion device 702 with oxygen gas 718 once an appendage is locatedwithin the interior space 714 and a sealed interface is formed betweenthe appendage and the compression exertion device 702 via a sealingcomponent 726. The sealing component 726 can include, for example, aphysical seal, an adhesive material seal or the like. Gaseous oxygen canbe injected into the interior space 714 through the gas-charging inletconnector 717 and sealed therein under a predetermined pressure tominimize release of oxygen from the bio-available pressure distributionmedium. Preferably, the outer body 708 can have a given thicknesscapable of resisting expansion up to about 3 psi. Expansion cavityconnectors inlet 704 and outlet 711 provide for a connecting means to apressure source to provide precise impingement pressure of a pressuremedium within a first expansion cavity 732 after insertion of anappendage into the interior space 714 and sealing of the outer body 708thereon. Expansion cavity connectors inlet 703 and outlet 712 providefor replacement and or replenishment of the pressure distribution medium707 prior to or during commencement of the chemotherapy procedure.

An extension 722 of the joined outer body 708 and the cavity partition720 may be folded over and down until the appendage is inserted into thecompression exertion device 702 at that point in time the extension 722is folded upward after a protection member (not shown) on the sealingcomponent 726 is removed and sealed to the epidermal portion of theappendage after is located within the interior apace of the compressionexertion device 702. The extension 722 may include an additional sealingcomponent 727. In one or more embodiments, a strap 743 (e.g., hook andloop such as VELCRO) may be wrapped around and fastened to the outsideportion of the extension 722 to help maintain seal between the extension722 and the epidermal portion of the appendage during pressurization.The oxygen pressure distribution medium may be additionally supplied inthe kit with a dispenser filled with the aqueous pressure distributionmedium having a inter connectable means to the expansion cavityconnector.

In one or more embodiments, the compression exertion device and partsthereof can be made from a variety of man-made or natural rubbers,plastics and the like, having a hardness on the harness scale 00 of frombetween 10 to 90 and resistance to expansion from between about 10 mm hgand 155 mm hg.

In one or more embodiments, the compression exertion device may comprisea membrane for passage of oxygen while other parts may comprise wovennon-woven textile resistant to expansion.

In one or more embodiments, an aqueous bio-available oxygen pressuredistribution medium comprises a solution of water, comprising nanobubbles (preferably smaller than 200 nm), a water solution comprising amixture of at least one or more of water, urea, glycol, ethanol, taurineto name a few and nano oxygen bubbles therein providing thereby a safeepidermal penetrating aqueous oxygen carrier providing diffusion ofoxygen into the epidermal skin layer and into the dermis skin layer andtissues therein, an oxygen charged perfluorocarbon composition.

In one or more embodiments, the pressure distribution medium ispressurized from between about 10 mm hg and 50 mm hg and is in intimatecontact with the epidermal skin layer for the duration of thechemotherapy treatment without a cyclical operation.

In one or more embodiments, the aqueous pressure distribution medium ispressurized from between about 10 mm hg and 50 mm hg and is in intimatecontact with the epidermal skin layer for the duration of thechemotherapy treatment without a cyclical operation.

As can be seen from the above disclosures, devices, systems and methodsin accordance with one or more embodiments of the present invention arespecifically adapted to provide intermittent displacement of blood tomitigate peripheral nerve neuropathy generally and chemotherapy-inducedneuropathy more specifically. Such devices, systems and methods areconfigured to enable precise, uniform and controlled blood displacingcompression of a patient’s appendage (e.g., hand(s), foot(feet) and thelike) This precise, uniform and controlled blood displacing compressionis imparted upon the epidermal and dermis skin layers of a patient’sappendage(s) to decrease the time that free nerve endings located in theepidermal and encapsulated nerve endings located in the dermis skinlayers are exposed to nerve damaging chemotherapy chemicals. To furtherlimit peripheral nerve neuropathy, in combination with theaforementioned controlled blood-occluding compression, devices, systemsand methods in accordance with one or more embodiments of the presentinvention can be adapted to simultaneously provide an oxygen supply tothe nerve endings through an aqueous oxygen containing medium (e.g., anoxygen containing pressure distribution medium). In this regard,embodiments of the present invention cause distributed compression thatdisplaces and at least partially occludes the blood supply to the dermisand epidermal skin layer that are highly susceptible to the damagecaused by chemotherapeutic agents while actively mitigating tissuedamage resulting from blood-occluding compression thereof. Below arefurther disclosures directed to devices, systems and methods inaccordance with one or more embodiments of the present invention.

In one or more embodiments, a compression exertion device is providedhaving an outer enclosure enclosing about at least a portion of the feetor hands (i.e., appendages). An expansion limiting impediment can befixed and enclosed about the outer enclosure to limit the outwardexpansion of the outer enclosure. The outer enclosure can comprise anexpansion cavity partition conforming to the inner surface of the outerenclosure and sealed about an opening in the outer enclosure forinsertion of an appendage.

In one or more embodiments, a system is provided having a programablecontrolled pressure source adapted to introduce a compression inducingmedium (fluid or gas) in to an expansion cavity of a compressionexertion device for achieving controlled intermittent inflation of theexpansion cavity when the compression inducing medium is introduced andpressurized within the expansion cavity from the programable controlledpressure source. The expansion cavity partition when pressurized,inflates and expands towards the epidermal skin portion of an appendageinserted within the opening of the outer enclosure, expanding away fromthe inside surface of the outer enclosure to the direction of theepidermal skin surface, adjacent to the inside surface of the expansioncavity partition. The pressure distribution article is of a flexibleform fitting material contoured to the irregular surface features of thefeet and hands and the inside portion of the expansion cavity partition.The expansion cavity partition when controllably inflated with a gas orliquid will cause a timed, temperature controlled and regulated pressureto be impinged upon the pressure distribution medium article and causesubstantially uniform compression of the irregular surface features ofat least a portion of the epidermal skin layer of the appendage,displacing blood within the dermis skin layers and one of at leastpartially occluding or complete occlusion of capillary blood vesselssupplying blood to the nerve endings within the dermis skin layer, andthereby at least partially occludes capillary blood vessels supplingblood to the nerve endings in the dermis skin layer, until apredetermined time of blood displacement and capillary blood vesselocclusion has passed. The cycle of compression begins prior tocommencement of the chemotherapy treatment. After a predetermined timeof compression, the programable controlled pressure source device canreturn pressure within the expansion cavity from between the 50 mm hgand 25 mm hg high pressure to atmospheric pressure for a predeterminedtime, allowing blood oxygen supply to the dermis skin layers, preventingdamage to skin tissues and nerve endings for lack of blood oxygensupply. Blood is allowed to circulate for a predetermined time toreplenish human tissue with oxygen and the cycle is then repeated asneeded.

In one or more embodiments, a self-contouring pressure distributionarticle (e.g., flowable or non-flowable medium) comprising a gas orliquid is provided for uniformly compressing irregular surface featuresof at least a portion of the appendage(s). Additionally, theself-contouring pressure distribution medium can be formulated tocomprise an oxygen enriched air or liquid, fluid, gel, cream, serum,paste and provides simultaneous epidermal and dermis skin compressionand facilitates diffusion of oxygen into at least portion of epidermaland dermis skin tissues of the appendage(s) during compression anddisplacement of blood within the dermis skin layer of the appendage. Theself- contouring pressure distribution medium being in contact with theepidermal skin portion of at least a portion of the appendage(s) resultsin oxygen being diffused through the epidermal skin layer.

In one or more embodiments, an expansion limiting impediment can befixed and bound about the outer enclosure to impede outward expansion ofthe outer enclosure.

In one or more embodiments, a flexible expansion cavity partition can befixed and sealed to form an expansion cavity, whereby the expansioncavity partition expands toward an exterior surface of the appendageduring pressurization of the compression-inducing medium by aninterconnected programable controlled pressure source into the expansioncavity, thereby expanding the expansion cavity partition toward theappendage and thereby pressure is impinged upon the pressuredistribution article and/or the self-contouring pressure distributionmedium to uniformly compress irregular epidermal surface features of theappendage(s).

In one or more embodiments, one or more penetration enhancers within anaqueous bio-available oxygen solution can be utilized to modify thestratum corium prior to or in combination with the components of theself-contouring pressure distribution medium of the present invention.The compression of the epidermal and dermis skin layers with the self-contouring pressure distribution medium can comprise an oxygen carrierthat includes at least one of a penetration enhancer, one or more oxygencharged perfluorocarbon compositions with preference to aperfluorodecalin, one or more pharmaceutical grade emulsifiers, one ormore surfactants, water formulated into a fluid, gel, serum, cream orthe like. Formulations of fluorocarbon oxygen carriers, surfactants,emulsions and penetration enhancers facilitates oxygen diffusion intoand through the stratum corium into the dermis skin layer, therebycausing diffusion of oxygen supply to peripheral nerve endings and skintissue during the time blood is being displaced and at least partiallyoccluded from the dermis skin layer.

In one or more embodiments, the self-contouring pressure distributionmedium can comprise nano sized oxygen bubbles in thermally conditionedwater and is replaced between cycles of compression and decompression ofthe self-contouring pressure distribution medium (e.g., thecompression-inducing medium) thereby displacing from within the outerenclosure previously utilized thermally conditioned water comprisingnano sized dissolved oxygen (i.e., a self-contouring pressuredistribution medium) and replacing with fresh thermally conditionedwater comprising nano-sized dissolved oxygen to thereby maintain highlevels of oxygen available for diffusion through the stratum corium andinto the dermis skin layer.

In one or more embodiments, a sealing component of a compressionexertion device is provided for sealing between the outer enclosure andthe epidermal skin surface of an appendage, where the sealing componentcan be an applied adhesive, a dual sided adhesive tape, a tackycompressible rubber or the like.

In one or more embodiments, the compression exertion device is providedwith at least one of a pressure sensor and a blood oxygen sensor infunctional contact with the appendage for enabling monitoring ofpressure exerted on the appendage and a blood oxygen level within theappendage and enable adjustment of system parameters to affect suchpressure and/or blood oxygen level.

In one or more embodiments, a pressure exertion device may be fittedwith an negative electrode portion of an iontophoresis device andconnecting means within the compression cavity adjacent to the epidermalshin of the appendage. The negative electrode can be shaped to match aninside portion of the pressure excretion device. The negative electrodeof the iontophoresis device can be covered with a pressure distributionmedium solution of nano oxygen bubble water that is premixed with watercompatible penetration enhancers, nano bubble stabilizers such asanionic surfactants and minerals to slightly increase the alkalinity ofthe aqueous pressure distribution solution. The nano oxygen bubbles arenegatively charged and saturated throughout the pressure distributionmedium. A positive electrode can be attached to a portion of theappendage away from the pressure exertion devise. The negative electrodecan repel the negatively charged nano oxygen bubbles away from thenegative electrode and pushes the nano oxygen bubbles into the epidermalskin layer being pushed by the negative electrical force and attractedby the positive electrical force of the positive electrode as currentand voltage are applied to the electrodes and thereby provides oxygendiffusion to tissues and nerves within the epidermal and dermis skinlayers during the pressure cycle of the pressure excursion device.

Although the invention has been described with reference to severalexemplary embodiments, it is understood that the words that have beenused are words of description and illustration, rather than words oflimitation. Changes may be made within the purview of the appendedclaims, as presently stated and as amended, without departing from thescope and spirit of the invention in all its aspects. Although theinvention has been described with reference to particular means,materials and embodiments, the invention is not intended to be limitedto the particulars disclosed; rather, the invention extends to allfunctionally equivalent technologies, structures, methods and uses suchas are within the scope of the appended claims.

What is claimed is:
 1. An apparatus for controlling operationalparameters of a compression exertion device having a body part of apatient disposed within a body part receiving space thereof, theapparatus being operable for: delivering a compression-inducing mediuminto one or more passages at least partially encompassing the body partreceiving space of the compression exertion device; pressurizing thecompression-inducing medium in conjunction with said delivering forexerting a compressive pressure by the compression exertion device onthe body part; thermally conditioning the compression-inducing medium inconjunction with said delivering; and performing, for limiting exposureof at least one of dermis tissue and peripheral nerves within the bodypart to chemotherapy chemicals within a blood supply of the patient, atleast one of said delivering, said pressurizing and said thermalconditioning at least partially based upon at least one treatmentparameter associated with treating the patient with a chemotherapeuticagent.
 2. The apparatus of claim 1 wherein said pressurizing and saidthermally conditioning are performed in conjunction with each other. 3.The apparatus of claim 1 wherein said delivering includes causing thecompression-inducing medium to flow through the one or more passages. 4.The apparatus of claim 3 wherein said causing the compression inducingmedium to flow through the one or more passages includes causing thecompression inducing medium to flow continuously at controlled pressureand temperature.
 5. The apparatus of claim 1 wherein said thermallyconditioning includes thermally conditioning the compression-inducingmedium to a temperature between 33° F. and a body temperature of thepatient.
 6. The apparatus of claim 1 wherein performing the at least oneof said delivering, pressurizing and thermal conditioning at leastpartially based upon the at least one treatment parameter associatedwith treating the patient with the chemotherapeutic agent includesperforming a combination of said delivering, pressurizing, and thermalconditioning at least partially based upon the at least one treatmentparameter associated with treating the patient with the chemotherapeuticagent.
 7. The apparatus of claim 1 wherein performing the at least oneof said delivering, pressurizing and thermal conditioning at leastpartially based upon the treatment parameter associated with treatingthe patient with the chemotherapeutic agent includes performing saiddelivering, pressurizing, and thermal conditioning at least partiallybased upon the at least one treatment parameter associated with treatingthe patient with the chemotherapeutic agent.
 8. The apparatus of claim1, further comprising: monitoring at least one of a compressivepressure, blood pressure, a blood flow, and a blood oxygen level of thepatient, wherein the at least one treatment parameter includes at leastone of the compressive pressure, blood pressure, blood flow, and bloodoxygen level.
 9. The apparatus of claim 8 wherein performing the atleast one of said delivering, pressurizing and thermal conditioning atleast partially based upon at least one treatment parameter associatedwith treating the patient with a chemotherapeutic agent includescontrolling at least said pressurizing the compression-inducing mediumbased at least partially upon at least one of the compressive pressure,blood pressure, blood flow, and blood oxygen level.
 10. The apparatus ofclaim 1 wherein said pressurizing includes maintaining thecompression-inducing medium at a pressure of sufficient magnitude andfor a sufficient magnitude to cause a reduction in blood flow to dermistissue and peripheral nerves within the body part.
 11. The apparatus ofclaim 10 wherein maintaining the compression-inducing medium at apressure of sufficient magnitude and for a sufficient magnitude to causea reduction in blood flow to dermis tissue and peripheral nerves withinthe body part is performed intermittently to temporarily allow anincreased amount of blood flow relative to the reduction in blood flow.12. The apparatus of claim 10 wherein said maintaining includesmaintaining the compression-inducing medium at a pressure of sufficientmagnitude for a sufficient duration of time to reduce blood flow withinat least a portion of the body part relative to the reduction in bloodflow by at least one of about 100% or less, 95% or less, 90% or less,75% or less, about 95%-90%, about 90%-75%, not less than about 75%, andnot less than about 50%.
 13. The apparatus of claim 12, furthercomprising: monitoring at least one of a compressive pressure, bloodpressure, a blood flow, and a blood oxygen level, of the patient,wherein the at least one treatment parameter includes at least one ofthe compressive pressure, blood pressure, blood flow, and blood oxygenlevel to enable control of blood flow.
 14. The apparatus of claim 1,further comprising: monitoring at least one of a compressive pressure,blood pressure, a blood flow, and a blood oxygen level of the patient,wherein the at least one treatment parameter includes at least one ofthe compressive pressure, blood pressure, blood flow, and blood oxygenlevel to enable control of blood flow within the body part.
 15. Theapparatus of claim 1 wherein said pressurizing includes maintaining thecompression-inducing medium in a pressure range sufficient for at leastreducing blood flow within dermis tissue of at least a portion of thebody part in response to compressive force exerted onto skin of the bodypart by the compression exertion device.
 16. The apparatus of claim 15wherein said maintaining includes maintaining the compression-inducingmedium at a pressure of sufficient magnitude for a sufficient durationof time to reduce blood flow within at least a portion of the body partrelative to the reduction in blood flow by at least one of about 100% orless, 95% or less, 90% or less, 75% or less, about 95%-90%, about90%-75%, not less than about 75%, and not less than about 50%.
 17. Theapparatus of claim 16, further comprising: monitoring at least one of acompressive pressure, blood pressure, a blood flow, and a blood oxygenlevel of the patient, wherein the at least one treatment parameterincludes at least one of the compressive pressure, blood pressure, bloodflow, blood oxygen level to enable control of blood flow.
 18. Theapparatus of claim 17 wherein maintaining the compression-inducingmedium in a pressure range sufficient for at least reducing blood flowwithin dermis tissue of at least a portion of the body part is performedintermittently to temporarily allow an increased amount of blood flowrelative to the reduction in blood flow.
 19. The apparatus of claim 15wherein maintaining the compression-inducing medium in a pressure rangesufficient for at least reducing blood flow within dermis tissue of atleast a portion of the body part is performed intermittently totemporarily allow an increased amount of blood flow relative to thereduction in blood flow.
 20. The apparatus of claim 19 whereinmaintaining the compression-inducing medium in a pressure rangesufficient for at least reducing blood flow within dermis tissue of atleast a portion of the body part in response to compressive forceexerted onto skin of the body part by the compression exertion deviceincludes maintaining the compression-inducing medium at a pressure ofsufficient magnitude for a sufficient duration of time to cause bloodflow within the body part to be reduced by at least one of about 100% orless, 95% or less, 90% or less, 75% or less, about 95%-90%, about90%-75%, not less than about 75%, and not less than about 50%.
 21. Theapparatus of claim 15 wherein said thermally conditioning includesthermally conditioning the compression-inducing medium to a temperaturebetween 33° F. and a body temperature of the patient.
 22. The apparatusof claim 21, further comprising: monitoring at least one of acompressive pressure, blood pressure, a blood flow, and a blood oxygenlevel of the patient, wherein the at least one treatment parameterincludes at least one of the compressive pressure, blood pressure, bloodflow, and blood oxygen level to enable control of blood flow.
 23. Theapparatus of claim 21 wherein maintaining the compression-inducingmedium in a pressure range sufficient for at least reducing blood flowwithin dermis tissue of at least a portion of the body part is performedintermittently to temporarily allow an increased amount of blood flowrelative to the reduction in blood flow.
 24. The apparatus of claim 23wherein maintaining the compression-inducing medium in a pressure rangesufficient for at least reducing blood flow within dermis tissue of atleast a portion of the body part includes maintaining thecompression-inducing medium at a pressure of sufficient magnitude for asufficient duration of time to cause blood flow within the at least aportion of body part to be reduced by at least one of about 100% orless, 95% or less, 90% or less, 75% or less, about 95%-90%, about90%-75%, not less than about 75%, and not less than about 50%.
 25. Theapparatus of claim 15, further comprising: monitoring output of at leastone sensor to obtain information characterizing at least one of acompressive pressure, blood pressure, a blood flow, and a blood oxygenlevel of the patient, wherein the at least one treatment parameterincludes at least one of the compressive pressure, blood pressure, bloodflow, and blood oxygen level and wherein said pressurizing is performedat least partially upon at least one of the compressive pressure, bloodpressure, blood flow, and blood oxygen level.
 26. The apparatus of claim1 wherein said pressurizing is paused intermittently to enable saiddelivering of the compression-inducing medium.
 27. The apparatus ofclaim 26 wherein said pressurizing includes maintaining thecompression-inducing medium in the pressure range sufficient for atleast reducing blood flow within dermis tissue of at least a portion ofthe body part via compressive force exerted onto skin of the body partby the compression exertion device.
 28. The apparatus of claim 27wherein performing the at least one of said delivering, pressurizing andthermal conditioning at least partially based upon the at least onetreatment parameter associated with treating the patient with thechemotherapeutic agent includes performing a combination of saiddelivering, pressurizing, and thermal conditioning at least partiallybased upon the at least one treatment parameter associated with treatingthe patient with the chemotherapeutic agent.
 29. The apparatus of claim27 wherein said pressurizing is performed for maintaining thecompression-inducing medium at a pressure of sufficient magnitude for asufficient duration of time to cause blood flow within at least aportion of the body part to be reduced by at least one of about 100% orless, 95% or less, 90% or less, 75% or less, about 95%-90%, about90%-75%, not less than about 75%, and not less than about 50%.
 30. Theapparatus of claim 29, further comprising: monitoring at least one of acompressive pressure, blood pressure, a blood flow, and a blood oxygenlevel of the patient, wherein the at least one treatment parameterincludes at least one of the compressive pressure, blood pressure, bloodflow, and blood oxygen level to enable control of blood flow.
 31. Theapparatus of claim 30 wherein said thermally conditioning includesthermally conditioning the compression-inducing medium to a temperaturebetween 33° F. and a body temperature of the patient.
 32. The apparatusof claim 1 wherein controlling operational parameters of a compressionexertion device includes an apparatuses for controlling, one ofindependently and simultaneously, at least one of pressure, flow,thermal conditioning, oxygen concentration, timed pressured anddepressurized sequences of fluids to said expansion cavity and saidpressure distribution medium receiving cavity.